The role of GABA, catecholamine and endorphins in the response of hypothalamus to different psychoactive drugs was studied by monitoring pituitary hormone release. Endogenous opiates stimulate PRL and block FSH release by activation of hypothalamic opiate receptors. These opiate receptors may be located on cells containing prolactin releasing factors since median eminence DA neurons or serotoninergic neurons apparently do not mediate the effects of morphine. Stimulation of hypothalamic or brain GABA receptors with muscimol fails to block morphine or haloperidol-induced PRL release. In contrast stimulation of GABA receptors in anterior pituitary prevents the morphine or haloperidol-induced PRL release. GABA receptors with characteristics similar to those of rat were observed also in human anterior pituitary. This suggests a possible physiological role of pituitary GABA receptors in the release of PRL.